The mouse Gene Expression Database (GXD): 2014 update

Constance M. Smith 0 Jacqueline H. Finger 0 Terry F. Hayamizu 0 Ingeborg J. McCright 0 Jingxia Xu 0 Joanne Berghout 0 Jeff Campbell 0 Lori E. Corbani 0 Kim L. Forthofer 0 Pete J. Frost 0 Dave Miers 0 David R. Shaw 0 Kevin R. Stone 0 Janan T. Eppig 0 James A. Kadin 0 Joel E. Richardson 0 Martin Ringwald 0 0 The Jackson Laboratory , 600 Main Street, Bar Harbor, ME 04609, USA The Gene Expression Database (GXD; http://www. informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental expression information. GXD collects different types of expression data from studies of wild-type and mutant mice, covering all developmental stages and including data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments. The data are acquired from the scientific literature and from researchers, including groups doing largescale expression studies. Integration with the other data in Mouse Genome Informatics (MGI) and interconnections with other databases places GXD's gene expression information in the larger biological and biomedical context. Since the last report, the utility of GXD has been greatly enhanced by the addition of new data and by the implementation of more powerful and versatile search and display features. Web interface enhancements include the capability to search for expression data for genes associated with specific phenotypes and/or human diseases; new, more interactive data summaries; easy downloading of data; direct searches of expression images via associated metadata; and new displays that combine image data and their associated annotations. At present, GXD includes >1.4 million expression results and 250 000 images that are accessible to our search tools. - INTRODUCTION The laboratory mouse serves as a premier animal model in studying the complex molecular mechanisms that underlie the processes of human development, differentiation and disease. Tissues from all stages of mouse development and from many different mouse strains and mutants are being subjected to detailed expression analysis. The Gene Expression Database (GXD) collects these data from disparate sources, integrates them and makes them readily accessible to many types of biologically and biomedically relevant database searches. By capturing multiple types of mRNA and protein expression information, including data from RNA in situ hybridization, immunohistochemistry, in situ reporter (knock in), reverse transcriptase-polymerase chain reaction (RT-PCR), northern blot and western blot experiments, GXD aims to provide increasingly complete information about where, when and in what amounts transcripts and proteins are expressed during development, as well as how their expression varies in different mouse strains and mutants. Data are acquired from the literature and from researchers, in particular from groups doing large-scale expression studies. All these data are annotated by GXD curators, making extensive use of controlled vocabularies and ontologies to provide the standardization of data that enables data integration and thereby complex queries. GXD forms an integral component of the larger Mouse Genome Informatics (MGI) resource. Through this association, the expression data can be combined with extensive genetic, functional, phenotypic and disease-orientated data (1). This robust integration, as well as interconnections with other resources (216), puts the expression data in GXD into a much larger analytical context. Owing to its broad scope, thorough approach, data integration and querying capabilities, GXD provides an important and unique resource to the research community. GXD and its user interfaces have been described previously (1720). Here we focus on recent progress in terms of data acquisition and improvements to the querying capabilities and web displays. DATA CONTENT AND PROGRESS IN DATA ACQUISITION Detailed expression data GXD provides detailed records of expression results. The core entry is an assay details record (Figure 1). Each assay details record includes information about the gene studied, the probes and experimental conditions used, the specimen(s) analyzed, the expression results obtained for each specimen, as well as images of the data when available. These data are annotated using standard nomenclature and ontologies and serve as integration points within the GXD and MGI database. Expression patterns are described using an extensive, hierarchically structured anatomical ontology. As well as allowing for the integration of expression results from assays with differing spatial resolution, the hierarchical nature of the ontology allows expression searches by anatomical term to include all substructures for the term. The developmental portion of the anatomical ontology was begun by our collaborators from the eMouseAtlas project (21) and is being extended and refined jointly with GXD; the postnatal part was developed by the GXD project (22). Genes studied in expression references Genes with expression assay results Expression assays Expression assay results Expression images Mouse mutants with expression data Since our last report, the amount of expression data in GXD has increased significantly both due to the GXD curators annotation of data from the literature and through the incorporation of data obtained from largescale expression projects. In all cases, the curators review the data and standardize it. When necessary, they work with laboratories to resolve issues pertinent to nomenclature and data inconsistencies. The most recently acquired large data sets include RNA in situ studies of gene expression in the day 14.5 embryo [GenePaint; (23)]; RNA in situ and immunohistochemistry studies of gene expression in the genitourinary tract [GUDMAP; (24)]; and RNA in situ studies of gene expression in the embryonic and adult mouse nervous system [BGEM; (25)]. The integration of these data into GXD greatly expands the research communitys ability to query these data, increasing their utility. As shown in Table 1, GXD currently contains detailed expression data for nearly 13 800 genes. There are 1.4 million expression result annotations; 82% are from RNA in situ hybridization studies and 10% from RTPCR studies. These results include data from >1850 mouse mutants, as well as numerous strains of wild-type mice. In addition, the database contains >250 000 images of primary expression data. Comprehensive literature survey GXD maintains a comprehensive and up-to-date index of the embryonic gene expression literature that can be searched using the Gene Expression Literature query (http://www.informatics.jax.org/gxdlit). The curators survey journals to find all published articles that describe endogenous gene expression and knock-in reporter studies done in the embryonic mouse. They then review the entire publication, including any supplemental material, and record the genes and ages ana (...truncated)